LBA6_PR - Hera Trial: 2 Years Versus 1 Year of Trastuzumab After Adjuvant Chemotherapy in Women with Her2-Positive Early Breast Cancer at 8 Years of Median Follow up

Abstract

ABSTRACT Background One year (yr) of trastuzumab (T) significantly improves disease-free (DFS) and overall survival (OS) in patients with HER2-positive early breast cancer (EBC) and is considered the standard of care. HERA is the only randomized trial investigating whether longer duration of T can further improve efficacy outcome. Materials and methods HERA (BIG 01-01) is an international, multicenter, phase III randomized trial involving 5102 women with HER2-positive EBC. Pts were randomized, after completion of primary therapy [surgery, chemotherapy and radiotherapy as indicated], to T every 3 weeks for 1 yr, 2 years (yrs), or observation. This landmark efficacy analysis compares the outcome of pts randomized to either 2 yrs or 1 yr of T who were disease-free at 1 yr after randomization (N = 1553 for 2 yrs, and N = 1552 for 1 yr). The primary endpoint is DFS and secondary endpoints are OS and time to distant recurrence (TTDR). Updated efficacy analyses of the T arms vs. observation at 8-yrs of median follow-up (FU) are also presented. Results On 12 April 2012 HERA reached the target number of 725 DFS events needed for 80% power to detect a true hazard ratio (HR) of 0.80 for the comparison of 2 yrs vs. 1 yr of T. The unadjusted HR for an event in the 2-yr vs. 1-yr T arms was 0.99 (95% CI 0.85-1.14; P = 0.8588). OS in the two arms was comparable [HR = 1.05 (95% CI 0.86-1.28; P = 0.6333)]. TTDR results were similar. The primary cardiac endpoint* was comparable (0.96% vs. 0.83% for 2-yr and 1-yr arms, respectively), but the secondary cardiac endpoint** was higher in the 2-yr arm (7.17% vs. 4.10%). Importantly, the durable benefit in DFS and OS for both 1 yr and 2 yrs of T compared with observation remains stable at 8 yrs of median FU. Conclusions These results confirm that 1 yr of adjuvant T remains the standard of care for HER2-positive EBC pts. It is also reassuring that the significant improvement in DFS and OS persists over time and that the incidence of cardiac endpoints remains low at a median FU of 8 yrs. *Cardiac death or severe CHF (NYHA class III or IV, confirmed by a cardiologist, and a significant LVEF decrease) ** An absolute decline ≥10% points from baseline LVEF and to Disclosure M. Piccart: Roche - Genentech: Consultancy, honoraria M. Procter: Marion Procter's institution has received funding in relation to the HERA trial E. De Azambuja: I have received travel grant form Roche. I have received honoraria from Roche. H. Weber: Stock options from Roche, Employment from Roche I.E. Smith: Honoraria from Roche L. Gianni: Roche: Advisory board, GSK: Advisory board C. Jackisch: Speakers Bureau Roche & GlaxoSmithKline D. Cameron: Personal and institutional reimbursement from Roche for advisory boards, consultancy and grants. M. Dowsett: Roche: Grant, advisory board, lecture fees J. Baselga: Advisory board memberships of Roche and GlaxoSmithKline. All other authors have declared no conflicts of interest.